Insulins are made up of two polypeptide chains, the A chain containing 21 amino acid residues and the B chain containing 30 amino acid residues. The A and B chains are bonded to one another via two disulfide bridges, the cysteine residues in positions A7 and B7 and in positions A20 and B19 being linked together. A third disulfide bridge exists between A6 and All. Animal and human insulins are formed in the pancreata as preproinsulins. Human preproinsulin is made up of a prepeptide containing 24 amino acid residues connected to a proinsulin containing 86 amino acid residues and has the following configuration: prepeptide-B-Arg-Arg-C-Lys-Arg-A, C being an amino acid chain containing 31 residues. During excretion from the Langerhans' islands, the prepeptide is cleaved and proinsulin is formed. Finally the C chain is cleaved by proteolysis and the effective human insulin is formed.
Insulin has many actions on insulin-sensitive tissue. One striking effect is the rapid reduction of the blood glucose level in mammals when insulin is administered. This is caused by a rapid uptake of glucose from the blood by muscle and fat cells. Insulin also activates glycogen synthetase and inhibits lipolysis. Insulin promotes protein synthesis from amino acids, increases the induction of glycokinase and phosphofructokinase and inhibits the formation of certain enzymes of gluconeogenesis, such as pyruvate carboxylase and fructose diphosphatase.
Type II diabetes, or insulin-independent diabetes, is associated with insulin resistance of the peripheral tissues such as muscle or fat tissues. The consequent reduction in glucose utilization is caused by the absence of insulin stimulation of the glucose transport and subsequent metabolic processes. This multiple resistance suggests a defect at receptor or postreceptor level, i.e. before production of the second messenger (Garvey, Diabetes/Metabolism Reviews 5 (1989) 727-742).
Peptides with an insulin-like action have already been disclosed in German patent applications P 40 40 574.5 and P 41 27 495.4.